The FilmArray 2.0 is an automated in vitro diagnostic (IVD) device designed to work with specific FilmArray reagent panels to detect multiple nucleic acid targets contained in clinical specimens. The FilmArray 2.0 instrument interacts with a reagent pouch to both purify nucleic acids and amplify targeted nucleic acid sequences using nested multiplex PCR in a closed system. The resulting PCR products are evaluated using DNA melting analysis. The FilmArray 2.0 software automatically determines the results and provides a test report.

The FilmArray 2.0 permits up to eight instruments to connect to one computer. This configuration reduces the space requirements for the system and offers centralized data management. Accessories for the FilmArray 2.0 include a computer stand and printer, a barcode scanner, an external Ethernet switch that allows several instruments to connect to a single computer, and an optional modular rack system to stack two instruments.

The main functions of the FilmArray 2.0 are as follows:

Moving liquids within the pouch and delivering rehydrated reagents in a specified . sequence to drive the nucleic acid purification and PCR amplification reactions.
. Heating and cooling to drive the PCR reactions and DNA melting.
. Capturing and processing of fluorescence images for analysis by the software.
. Automated data interpretation and test report generation.

AI/ML Overview

The FilmArray 2.0 device is an automated in vitro diagnostic (IVD) device designed for use with FilmArray panels to detect multiple nucleic acid targets in clinical specimens. The device's performance was evaluated through a series of studies comparing it to the previously cleared FilmArray device (K103175).

1. Table of Acceptance Criteria and Reported Device Performance:

The document does not explicitly list "acceptance criteria" in a numerical format that can be directly compared to reported device performance. However, the summary of performance data indicates that the device was deemed substantially equivalent to its predicate. The functional equivalence implies that the performance of the FilmArray 2.0 met the expected performance standards demonstrated by the predicate device for various parameters.

Acceptance Criteria (Inferred from equivalence claim)	Reported Device Performance (FilmArray 2.0 vs. FilmArray, K103175)
Equivalent detection in clinical specimens	Performance of all three panels (RP, BCID, GI) was found to be equivalent on FilmArray 2.0 and the previously cleared FilmArray.
Equivalent detection of low analyte levels	Performance of all three panels (RP, BCID, GI) was found to be equivalent on FilmArray 2.0 and the previously cleared FilmArray.
Equivalent reproducibility	Performance of all three panels (RP, BCID, GI) was found to be equivalent on FilmArray 2.0 and the previously cleared FilmArray.

2. Sample size used for the test set and the data provenance:

The document mentions that each panel (Respiratory Panel (RP), Blood Culture Identification (BCID) Panel, and Gastrointestinal (GI) Panel) was evaluated in three types of studies:

Clinical specimen comparison study: Involved testing a set of clinical samples. The exact number of samples is not specified for this summary document, but it compares FilmArray 2.0 to the current FilmArray. The provenance (e.g., country of origin) is not specified, and the study type appears to be retrospective (using existing clinical samples).
Low analyte study: Compared the performance of the two devices by testing contrived samples spiked around the previously-determined limit of detection (LoD) for each assay on the panel. The number of contrived samples is not specified.
Reproducibility study: Involved testing a set of well-characterized contrived samples. The number of contrived samples is not specified. This study was conducted at three different testing sites over several days.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):

This information is not specified in the provided document. The device automatically interprets results, and the ground truth would likely be established through standard microbiology/molecular diagnostic methods against which the device's results are compared, rather than expert human interpretation of the device's raw output.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

This information is not specified in the provided document. Given the nature of an automated IVD device, the primary ground truth is usually established by a reference method, not by human adjudication of device outputs.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

A multi-reader multi-case (MRMC) comparative effectiveness study was not performed, nor is it applicable to this device. The FilmArray 2.0 is an automated instrument that provides a direct result without human interpretation of complex images or data that would necessitate a MRMC study. Its output is a test report.

6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done:

Yes, the studies described are inherently "standalone" in the sense that they evaluate the device's ability to autonomously detect nucleic acid targets and provide a test report. The device’s software automatically determines the results and provides a test report, indicating that a human is not in the loop for the primary result interpretation.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth for the test set would have been established using reference laboratory methods for detecting nucleic acid targets in clinical specimens, and potentially the established Limit of Detection (LoD) for contrived samples. For clinical studies, this would likely involve results from other FDA-cleared diagnostic tests or gold-standard laboratory techniques. The document mentions "well-characterized contrived samples", implying a known composition/presence of analytes.

8. The sample size for the training set:

The document describes performance studies for a medical device that has been developed. It does not provide information on a "training set" in the context of machine learning. The term "training set" is usually associated with the development of AI/ML algorithms. This device relies on established PCR and DNA melting analysis principles, with software interpreting these biophysical reactions. Therefore, there isn't a "training set" in the typical AI sense mentioned here.

9. How the ground truth for the training set was established:

As noted above, there is no mention of a "training set" in the context of AI/ML, as this device uses established molecular diagnostic techniques and software for interpretation. The software's "knowledge" is based on the expected melting curves and PCR amplification patterns of known targets, not on being trained on a dataset with ground truth labels in the same way a deep learning model would be.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

BIOFIRE DIAGNOSTICS, LLC KRISTEN KANACK, Ph.D. VICE PRESIDENT OF REGULATED PRODUCTS 390 WAKARA WAY SALT LAKE CITY UT 84108

January 30, 2015

Re: K143178

Trade/Device Name: FilmArrav 2.0 Regulation Number: 21 CFR 862.2570 Regulation Name: Instrumentation for clinical multiplex test systems Regulatory Class: II Product Code: NSU Dated: October 31, 2014 Received: November 4, 2014

Dear Dr. Kanack:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uwe Scherf -S for

Sally Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K143178

Device Name FilmArray 2.0

Indications for Use (Describe)

The FilmArray 2.0 is an automated in vitro diagnostic (IVD) device designed for use with FilmArray panels. The FilmArray 2.0 is intended for use in combination with assay specific reagent pouches to detect multiple nucleic acid targets contained in clinical specimens. The FilmArray 2.0 instrument interacts with the reagent pouch to both purify nucleic acids and amplify targeted nucleic acid sequences using nested multiplex PCR in a closed system. The resulting PCR products are evaluated using DNA melting analysis. The software automatically determines the results and provides a test report.

The FilmArray 2.0 is composed of one to eight instruments connected to a computer running FilmArray 2.0 software, which controls the function of each instrument and collects, and stores data generated by each instrument.

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary BioFire Diagnostics, LLC

FilmArrav® 2.0

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Submitted by:

BioFire Diagnostics, LLC 390 Wakara Way Salt Lake City, UT 84108

Telephone: 801-736-6354 Facsimile: 801-588-0507

Contact: Kristen Kanack, ext. 330

Date Submitted: October 31, 2014

Device Name and Classification:

Trade Name: FilmArray 2.0

Regulation Number: 21 CFR 862.2570

Classification Name: Instrumentation for clinical multiplex test systems

Predicate Device:

K103175 – FilmArray

Intended Use:

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Device Description:

The main functions of the FilmArray 2.0 are as follows:

Moving liquids within the pouch and delivering rehydrated reagents in a specified . sequence to drive the nucleic acid purification and PCR amplification reactions.
. Heating and cooling to drive the PCR reactions and DNA melting.
. Capturing and processing of fluorescence images for analysis by the software.
. Automated data interpretation and test report generation.

Principles of Operation:

A test is initiated by loading Hydration Solution into one port of the FilmArray pouch and a patient sample mixed with the provided Sample Buffer into the other port of a FilmArray pouch and placing it in the FilmArray instrument. The pouch contains all of the reagents required for specimen testing and analysis in a freeze-dried format; the addition of Hydration Solution and Sample/Buffer Mix rehydrates the reagents. After the pouch is prepared, the software guides the user though the steps of placing the pouch into the instrument, scanning the pouch barcode, entering the sample identification, and initiating the run.

The FilmArray 2.0 instrument contains a coordinated system of inflatable bladders and seal points, which act on the pouch to control the movement of liquid between the pouch blisters. When a bladder is inflated over a reagent blister. it forces liquid from the blister into connecting channels. Alternatively, when a seal is placed over a connecting channel it acts as a valve to open or close a channel. In addition, electronically controlled pneumatic pistons are positioned over multiple plungers in order to deliver the rehydrated reagents into the blisters at the appropriate times. Two Peltier devices control heating and cooling of the pouch to drive the PCR reactions and the melt curve analysis.

Nucleic acid extraction occurs within the FilmArray pouch using mechanical and chemical Iysis followed by purification using standard magnetic bead technology. The instrument has a built-in

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bead-beater to aid in mechanical lysis and a retractable magnet that is used to capture the magnetic beads used in the nucleic acid purification process. After extracting and purifying nucleic acids from the unprocessed sample, a nested multiplex PCR is executed in two stages. During the first stage, a single, large volume, highly-multiplexed PCR reaction is performed (including reverse transcription of RNA to DNA, when needed). The products from first stage PCR are then diluted and combined with a fresh, primer-free master mix and a fluorescent double stranded DNA binding dye (LC Green® Plus, BioFire Defense). The solution is then distributed to each well of the array. Array wells contain sets of primers designed specifically to amplify sequences internal to the PCR products generated during the first stage PCR reaction. The 200 stage PCR, or nested PCR, is performed in singleplex fashion in each well of the array. At the conclusion of the 2nd stage PCR, the array is interrogated by melt curve analysis for the detection of signature amplicons denoting the presence of specific targets. A digital camera placed in front of the 2nd stage PCR captures fluorescent images of the PCR reactions and software interprets the data.

The software automatically interprets the results of each DNA melt curve analysis and combines the data with the results of the internal pouch controls to provide a test result for each organism on the reagent panel.

Substantial Equivalence:

The FilmArray 2.0 is substantially equivalent to the current FilmArray device. The current FilmArray was cleared as a system with the FilmArray Respiratory Panel on February 17, 2011 under 510(k) K103175 and was determined to be a Class II device.

The following tables compare the FilmArray 2.0 to the current FilmArray device. Table 1 outlines the similarities and differences between the two devices.

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Element	Predicate:FilmArray (K103175)	New Device:FilmArrav 2.0
Intended Use	The FilmArray instrument is an automatedin vitro diagnostic (IVD) device designedto work with specific reagent pouches todetect multiple nucleic acid targetscontained in clinical specimens. Theinstrument interacts with the reagentpouch to both purify nucleic acids andamplify targeted nucleic acid sequencesusing nested multiplex PCR in a closedsystem. The resulting PCR products areevaluated using DNA melting analysis.The FilmArray software thenautomatically interprets the results andprovides an easy-to-understand test report.The FilmArray device is composed of theFilmArray instrument and a laptopcomputer loaded with FilmArray software.The instrument contains a series ofpneumatic actuators that move liquidwithin the pouch, a bead beater fordisrupting the specimen during nucleicacid purification, two Peltier devices todrive thermocycling and DNA melting,and an optics system for detectingfluorescent signals. The FilmArraysoftware controls the function of theinstrument and collects, stores, andanalyzes data generated by the instrument.	Same
Assays	For use with FDA cleared FilmArraypanels:Respiratory Panel (RP)Blood Culture Identification (BCID) PanelGastrointestinal (GI) Panel	Same
ProtocolProcessing Steps	Cell disruption, nucleic acid extraction,PCR1 thermocycling, PCR2thermocycling, DNA melt and signaldetection.	Same
Time to result	Approximately 1 hour per sample	Same
TechnologicalPrinciples	Nested multiplex nucleic acidamplification (including reversetranscription as appropriate) followed byhigh-resolution melting analysis toconfirm the identity of the amplifiedproduct.	Same
Element	Predicate:FilmArray (K103175)	New Device:FilmArray 2.0
RequiredAccessory	FilmArray reagent pouch	Same
SamplePreparationMethod	Minimal sample processing and hands-ontime.	Same
Test Interpretationand ResultsReporting	Automated test interpretation and reportgeneration. User cannot access raw data.Report can be printed.	Same
User Complexity	Moderate	Same
Instrument Optics	Charge-coupled device (CCD) camera.	Complimentary metal-oxidesemiconductor (CMOS) camera
	Soft-coated filters.	Hard-coated filters.
Instrument -SoftwareCommunication	Communication travels via Firewire andUSB cables/ports.	Communication travels via Ethernetcable/port.Communication for multiple instrumentsmediated by a multi-port switch.
Deviceconfiguration	One FilmArray instrument to one laptopcomputer with mouse, barcode scannerand pouch loading station.Single-sample test capacity.	Up to eight FilmArray 2.0 instruments toone computer with mouse, barcode scannerand pouch loading station.Single-sample test capacity per instrumentwith random-access multi-sample testcapacity per system.
	Printer optional.	Printer provided with the system.
	Instrument held at 0° angle.	Interlocking two-instrument racksavailable to stack instruments and reducesystem footprint. (Optional)Instrument held at 0° angle when no rackis used. Instrument held at 15° angle onrack.

Table 1. Comparison between FilmArray 2.0 and the Current FilmArray Device.

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Summary of Performance Data:

The performance of the FilmArray 2.0 was evaluated using three FDA cleared FilmArray Panels (Respiratory Panel (RP), Blood Culture Identification (BCID) Panel, and Gastrointestinal (GI) Panel). Each panel was evaluated in three studies, a clinical specimen comparison study, a low analyte study, and a reproducibility study. The clinical comparison study involved testing a set

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of clinical samples using both the current FilmArray 2.0. The low analyte study compared the performance of the two devices by testing contrived samples spiked around the previously-determined limit of detection (LoD) for each assay on the panel. The reproducibility study was conducted using multi-instrument FilmArray 2.0 systems and involved testing of a set of well-characterized contrived samples at three different testing sites over several days and comparing the results to those previously obtained with the current FilmArray device. In all studies (i.e., detection in clinical specimens, detection of low analyte levels, and reproducibility) the performance of all three panels was found to be equivalent on the previously cleared FilmArray and the FilmArray 2.0. Data generated in these studies are presented in three concurrently-submitted 510(k) premarket notifications.

Regulation Number and Section

§ 862.2570 Instrumentation for clinical multiplex test systems.

(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.